Models trained on nonpathogenic deletions in the general population reliably estimate the effect size of pathogenic deletions and suggest omnigenic associations of haploinsufficiency with IQ. This represents a new framework to study variants too rare to perform individual association studies and can help estimate the cognitive effect of undocumented deletions in the neurodevelopmental clinic.

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Mechanical stretch may promote endothelial-mesenchymal transition and pulmonary fibrosis through a NLRP3-dependent pathway. The inhibition of endothelial-mesenchymal transition by NLRP3 inactivation may be a viable therapeutic strategy against pulmonary fibrosis associated with mechanical ventilation.

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Mechanism by which α-synuclein affects the progression of Parkinson's disease through Pyrin Domain Containing Protein 3 (NLRP3) was explored. Peripheral blood plasma of 40 Parkinson's disease patients and 40 normal healthy people attending the department of neurology of the Third Affiliated Hospital of Qiqihar Medical University were collected from March 2018 to January 2019. The expression levels of oligomers, phosphorylated α-synuclein, interleukin-1β (IL-1β), interleukin-6 (IL-6) and transforming growth factor-α (TGF-α) in plasma were detected by ELISA. Astrocytes in mouse brain tissues were extracted by primary culture method, the cells were divided into drug group and the drug + inhibitor group. After adding 0, 5, 10 and 20 µg oligomerized α-synuclein or 5 mM autophagy inhibitor 3-Methyladenine (3-MA), the expression level of NLRP3, caspase-1, IL-1β and Atg5 proteins in the cells was detected. The expression level of IL-1β in peripheral blood of PD patients was significantly increased (0.604±0.136 µmol/l vs. 1.876±0.327 µmol/l, P=0.002), while there was no significant difference between IL-6 and TGF-α. Both oligomers (0.171±0.045 µmol/l vs. 0.676±0.084 µmol/l, P<0.0001) and phosphorylated α-synuclein (0.128±0.041 µmol/l vs. 0.849±0.108 µmol/l, P<0.0001) in peripheral blood of PD patients were significantly elevated. The expression levels of NLRP3, caspase-1 and IL-1β in mouse astrocytes all increased with the increase of the concentration of oligomerized α-synuclein, and Atg5 protein expression also increased gradually with the concentration, and reached the highest level when the concentration was 10 µg/ml. The expression levels of NLRP3, caspase-1 and IL-1β were inhibited after the addition of autophagy inhibitor 3-MA. α-synuclein mediates the activation of NLRP3 inflammasome in PD patients by up regulating Atg5 protein expression.

Recently, the lncRNA small nucleolar RNA host gene (SNHG1) has been exhibited to be upregulated, which plays a crucial role in the development and prognosis of several cancers. However, the role of the biology and clinical significance of SNHG1 in the tumorigenesis of colorectal cancer (CRC) has rarely been reported. In this work, we firstly found that SNHG1 expression levels were upregulated aberrantly in colorectal cancer tissues and colorectal cancer cell lines. By Kaplan-Meier survival analysis, patients with high SNHG1 expression level had poorer overall survival (OS) and progression-free survival (PFS) than those with low SNHG1 expression. In multivariate analysis, increased SNHG1 expression was proved to be an independent unfavorable prognostic indicator for CRC. In vitro experiments revealed that SNHG1 silencing inhibited the growth and metastasis and induced apoptosis of CRC cell lines. Finally, we found that SNHG1 may induce the activation of the WNT/β-catenin pathway through regulating β-catenin expression and transcription factor-4 (TCF-4), cyclin D1 and MMP-9. Altogether, our findings demonstrated that lncRNA SNHG1, was high expressed in colorectal cancer tissues and may serve as a tumor oncogene through regulating WNT/β-catenin signal pathway, which provided a candidate diagnostic biomarker and a promising therapeutic target for patients with CRC.